Biomedical subjects

L J Gershwin

Publications and source records attributed to L J Gershwin.

At least 19 recordsLinked to original sources

PubMed2006

Alternaria aerosol during a bovine respiratory syncytial virus infection alters the severity of subsequent re-infection and enhances IgE production.

BACKGROUND: Previous studies with cattle and rodent models have shown that bovine and human RSV infections influence the immune response to inhaled allergen. In the present study, we extended these observations to examine the effect of fungal allergen Alternaria alternata aerosol exposure (prior to and during BRSV infection) on the immune response and clinical outcome of a secondary BRSV infection. METHODS: Calves were either Alternaria (Alt)/mock Alt (mAlt) and BRSV/mBRSV exposed. Exposures began on day -6 and continued every other day until day 6 post infection. A second set of aerosols/infection began on day 103 and continued as before. Clinical outcome during infections was measured in each group. IgG1, IgA, and IgE responses to Alternaria were measured in serum or bronchiolar alveolar lavage fluid (BALF). Cytokine responses, including IL-4, were also measured. RESULTS: Alternaria did not influence primary infection; however, the Alt/BRSV group had less disease than mAlt/BRSV group (median clinical score 8 vs 476.5; p<or=0.01) after secondary infection. Exposure to Alternaria facilitated IgE antibody production in BRSV infected calves. IgE responses to Alternaria were higher in Alt/BRSV than Alt/mBRSV animals on day 10 (mean baseline fold increase 1.97 vs 1.06; p=0.013) and 109 (1.40 vs 0.810; p=0.008). Comparatively, Alt/BRSV calves had less Alternaria specific IgG1 than Alt/mBRSV calves on days 0, 107, 109, 113, 115, and 120 (p<or=0.05) with more lung eosinophils and IL-4 secreting PBMCs. CONCLUSION: Alternaria aerosols during primary and secondary BRSV infections decreased disease in secondary infections; however, BRSV infection enhanced Th2 responses against inhaled Alternaria.

Aerosols↗

PubMed2005

Airway generation-specific differences in the spatial distribution of immune cells and cytokines in allergen-challenged rhesus monkeys.

BACKGROUND: Accumulation of immune cell populations and their cytokine products within tracheobronchial airways contributes to the pathogenesis of allergic asthma. It has been postulated that peripheral regions of the lung play a more significant role than proximal airways with regard to inflammatory events and airflow obstruction. OBJECTIVE: To determine whether immune cell populations and associated cytokines are uniformly distributed throughout the conducting airway tree in a non-human primate model of allergic asthma. METHODS: We used a stereologic approach with a stratified sampling scheme to measure the volume density of immune cells within the epithelium and interstitium of trachea and 4-5 intrapulmonary airway generations from house dust mite (HDM) (Dermatophagoides farinae)-challenged adult monkeys. In conjunction with immune cell distribution profiles, mRNA levels for 21 cytokines/chemokines and three chemokine receptors were evaluated at four different airway generations from microdissected lungs. RESULTS: In HDM-challenged monkeys, the volume of CD1a+ dendritic cells, CD4+ T helper lymphocytes, CD25+ cells, IgE+ cells, eosinophils, and proliferating cells were significantly increased within airways. All five immune cell types accumulated within airways in unique patterns of distribution, suggesting compartmentalized responses with regard to trafficking. Although cytokine mRNA levels were elevated throughout the conducting airway tree of HDM-challenged animals, the distal airways (terminal and respiratory bronchioles) exhibited the most pronounced up-regulation. CONCLUSION: These findings demonstrate that key effector immune cell populations and cytokines associated with asthma differentially accumulate within distinct regions and compartments of tracheobronchial airways from allergen-challenged primates.

Animals↗

PubMed2005

Uterine mast cells and immunoglobulin-E antibody responses during clearance of Tritrichomonas foetus.

We showed earlier that Tritrichomonas foetus-specific bovine immunoglobulin (Ig)G1 and IgA antibodies in uterine and vaginal secretions are correlated with clearance of this sexually transmitted infection. Eosinophils have been noted in previous studies of bovine trichomoniasis but the role of mast cells and IgE responses have not been reported. The hypothesis that IgE and mast cell degranulation play a role in clearance was tested in 25 virgin heifers inseminated experimentally and infected intravaginally with T. foetus strain D1 at estrus and cultured weekly. Groups were euthanatized at 3, 6, 9, or 12 weeks, when tissues were fixed and secretions were collected for culture and antibody analysis. Immunohistochemistry using a monoclonal antibody to a soluble lipophosphoglycan (LPG)-containing surface antigen (TF1.17) demonstrated antigen uptake by uterine epithelial cells. Lymphoid nodules were detected below antigen-positive epithelium. Little IgG2 antibody was detected but IgG1, IgA, IgM, and IgE T. foetus-specific antibodies increased in uterine secretions at weeks 6 and 9 after infection. This was inversely proportional to subepithelial mast cells numbers and most animals cleared the infection by the sampling time after the lowest mast cell count. Furthermore, soluble antigen was found in uterine epithelium above inductive sites (lymphoid nodules). Cross-linking of IgE on mast cells by antigen and perhaps LPG triggering appears to have resulted in degranulation. Released cytokines may account for production of predominantly Th2 (IgG1 and IgE) and IgA antibody responses, which are related to clearance of the infection.

Animals↗

PubMed2004

Progress in defining the role of RSV in allergy and asthma: from clinical observations to animal models.

Respiratory syncytial virus (RSV), an RNA virus in the family Paramyxoviridae, causes respiratory disease in humans. A closely related bovine RSV is responsible for a remarkably similar disease syndrome in young cattle. Severe RSV disease is characterized by bronchiolitis. The impact of RSV on human health is demonstrated annually when infants are admitted to the hospital in large numbers. Nearly every child will have been infected with RSV by the age of 3 years. While the disease is most severe in young infants and elderly people, it can re-infect adults causing mild upper respiratory tract disease throughout life. In addition, there is growing evidence that RSV infection may also predispose some children to the development of asthma. This is based on the observation that children who wheeze with RSV-induced bronchiolitis are more likely to develop into allergic asthmatics. Recent studies describe attempts to create an RSV induced asthma model in mice and other species; these have shown some degree of success. Such reports of case studies and animal models have suggested a wide range of factors possibly contributing to RSV induced asthma, these include timing of RSV infection with respect to allergen exposure, prior allergic sensitization, environmental conditions, exposure to endotoxin, and the genetic background of the person or animal. Herein, we primarily focus on the influence of RSV infection and inhalation of extraneous substances (such as allergens or endotoxin) on development of allergic asthma.

Allergens↗

PubMed2004

The remodelled tracheal basement membrane zone of infant rhesus monkeys after 6 months of recovery.

BACKGROUND: In previous studies, we showed that repeated exposure to (1) house dust mite allergen (HDMA) (Dermatophagoides farinae) caused thickening of the basement membrane zone (BMZ) and (2) HDMA+ozone (O3) caused depletion of BMZ perlecan and atypical development of BMZ collagen (irregular thin areas<2.0 microm in width). OBJECTIVE: The purpose of this study was to determine if these remodelling changes were reversible after 6 months of recovery. METHODS: Rhesus monkeys were exposed to a regimen of HDMA and or O3 or filtered air (FA) for 6 months. After the exposure protocol was completed FA and O3 groups were allowed to recover in FA for 6 months. The HDMA and HDMA+O3 exposure groups recovered in a modified environment. They were re-exposed to HDMA aerosol for 2 h at monthly intervals during recovery in order to maintain sensitization for pulmonary function testing. To detect structural changes in the BMZ, collagen I and perlecan immunoreactivity were measured and compared to data from the previous papers. RESULTS: The remodelled HDMA group had a significantly thicker BMZ and after 6 months of recovery the width had not regressed. In the remodelled BMZ of the HDMA+O3 group, perlecan had returned to the BMZ after 6 months of the recovery protocol, and the thin, irregular, collagen BMZ had been resolved. CONCLUSION: In summary, this study has shown that: (1) The width of the remodelled HDMA BMZ did not regress during a recovery protocol that included a sensitizing dose of HDMA. (2) The atypical collagen BMZ in the HDMA+O3 BMZ was resolved in the absence of O3. (3) Depletion of perlecan from the BMZ by O3 was reversed by recovery in the absence of O3.

Animals↗

PubMed2004

Smooth muscle hypertrophy in distal airways of sensitized infant rhesus monkeys exposed to house dust mite allergen.

BACKGROUND: Airway smooth muscle hypertrophy is closely associated with the pathophysiology of hyper-reactive airways in allergic asthma. OBJECTIVE: To determine whether repeated exposure to allergens during postnatal lung development promotes remodelling of airway smooth muscle. METHODS: Infant, male rhesus monkeys (30-day-old) were sensitized to house dust mite allergen (HDMA) and then exposed to HDMA aerosol periodically over 5 months. Smooth muscle mass and bundle size and abundance in conducting airways were measured and compared with age-matched control (filtered air-exposed) monkeys. RESULTS: Total smooth muscle mass and average bundle size were significantly greater in the conducting airways of monkeys exposed to HDMA. Smooth muscle bundle abundance was not affected by exposure to HDMA. CONCLUSION: Repeated cycles of allergen exposure alter postnatal morphogenesis of smooth muscle, affecting both total mass and bundle size, in conducting airways of infant monkeys.

Allergens↗

PubMed2003

Allergen-specific IgG and IgA in serum and bronchoalveolar lavage fluid in a model of experimental feline asthma.

Allergic asthma, a Th2 cell driven response to inhaled allergens, has classically been thought of as predominantly mediated by IgE antibodies. To investigate the role of other immunoglobulin classes (e.g., IgG and IgA) in the immunopathogenesis of allergic asthma, levels of these allergen-specific immunoglobulins were measured in serum and mucosal fluids. Bermuda grass allergen (BGA)-specific IgG and IgA ELISAs in serum and bronchoalveolar lavage fluid (BALF) were developed and optimized in an experimental model of BGA-induced feline asthma. Levels of BGA-specific IgG and IgA significantly increased over time in serum and BALF after allergen sensitization. Additionally, these elevated levels of BGA-specific IgG and IgA were seen in conjunction with the development of an asthmatic phenotype indicated by positive intradermal skin tests, enhanced airways hyperreactivity, and increased eosinophil percentages in the BALF.

Allergens↗

PubMed2003

Production of polyclonal antisera against feline immunoglobulin E and its use in an ELISA in cats with experimentally induced asthma.

Serum samples from six cats with experimentally induced asthma were used to purify feline IgE using gel filtration and affinity chromatography. The resultant IgE, evaluated for purity by immunoelectrophoresis (IEP) and reactivity by Prausnitz-Kustner (PK) testing, was used to develop polyclonal rabbit anti-feline IgE antisera. Using reverse cutaneous anaphylaxis (RCA), the antisera were determined to be specific for feline IgE. The polyclonal rabbit anti-feline IgE antiserum was then validated in an allergen-specific ELISA. Serum samples from an additional five asthmatic cats sensitized with Bermuda grass allergen (BGA) were evaluated prior to sensitization, after parenteral sensitization, and after aerosol sensitization and challenge. A significant increase in serum BGA-specific IgE was noted over time.

Allergens↗

PubMed2003

Immune and airway effects of house dust mite aeroallergen exposures during postnatal development of the infant rhesus monkey.

BACKGROUND: The effect of chronic environmental aeroallergen exposure on the immune system and airways has not been experimentally defined in very young children. OBJECTIVE: The purpose of this study was to determine the immunophenotype of peripheral blood and airway leucocytes in the newborn rhesus macaque monkey, following recurrent aerosol exposure to house dust mite (HDM) (Dermatophagoides farinae). METHODS: A regimen of HDM aerosolization was initiated for 2 h per day, three times per week, starting when rhesus macaque monkeys were 1 week of age. All monkeys were inoculated with diptheria, tetanus, and acellular pertussis vaccine at 5 weeks of age to simulate human infant vaccination schedules. RESULTS: Following 8 weeks of HDM aeroallergen exposure, infant monkeys exhibited a significant reduction in the total peripheral blood lymphocyte numbers and a decreased frequency of peripheral blood CD4+ T lymphocytes with a CD45RA-'memory' immunophenotype. Lavage CD4+ T lymphocytes from HDM-exposed monkeys showed elevated expression of CD25, as well as an increase in CD45RA-/CD62L-/CD11ahigh immunophenotype. Eosinophils were more abundant within airways of HDM-exposed monkeys, accumulating maximally within the trachea. CONCLUSION: These data demonstrate the development of immunological responses following chronic inhalation of a common environmental allergen during postnatal maturation in the non-human primate.

Animals↗

PubMed2002

A rhesus monkey model of respiratory syncytial virus infection.

Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract disease in infants and young children worldwide. To date, there is no single animal model that adequately reproduces all human disease states. Here, we have developed a model of experimental infection with human RSV in infant Rhesus macaques. Infected animals demonstrated mild clinical disease including increased respiratory rates, fever and adventitious lung sounds. While more severe disease was not observed, preliminary virological and histopathological findings are promising. It is anticipated that with further optimization, this model will provide a useful system with which to study disease due to RSV infection and evaluate candidate vaccines.

Animals↗

PubMed2001

Allergic asthma induced in rhesus monkeys by house dust mite (Dermatophagoides farinae).

To establish whether allergic asthma could be induced experimentally in a nonhuman primate using a common human allergen, three female rhesus monkeys (Macaca mulatta) were sensitized with house dust mite (Dermatophagoides farinae) allergen (HDMA) by subcutaneous injection, followed by four intranasal sensitizations, and exposure to allergen aerosol 3 hours per day, 3 days per week for up to 13 weeks. Before aerosol challenge, all three monkeys skin-tested positive for HDMA. During aerosol challenge with HDMA, sensitized monkeys exhibited cough and rapid shallow breathing and increased airway resistance, which was reversed by albuterol aerosol treatment. Compared to nonsensitized monkeys, there was a fourfold reduction in the dose of histamine aerosol necessary to produce a 150% increase in airway resistance in sensitized monkeys. After aerosol challenge, serum levels of histamine were elevated in sensitized monkeys. Sensitized monkeys exhibited increased levels of HDMA-specific IgE in serum, numbers of eosinophils and exfoliated cells within lavage, and elevated CD25 expression on circulating CD4(+) lymphocytes. Intrapulmonary bronchi of sensitized monkeys had focal mucus cell hyperplasia, interstitial infiltrates of eosinophils, and thickening of the basement membrane zone. We conclude that a model of allergic asthma can be induced in rhesus monkeys using a protocol consisting of subcutaneous injection, intranasal instillation, and aerosol challenge with HDMA.

Animals↗

PubMed2001

Immunoglobulin E-mediated hypersensitivity in food-producing animals.

Type I hypersensitivity has been described as a cause of allergic reactivity to inhalants, injectables, endoparasites, and ectoparasites in food animal species. In addition, IgE is credited with showing some host-sparing effect when produced in response to certain gastrointestinal and other parasites. Recently, the sophistication of diagnostic procedures has increased with the elucidation of epsilon heavy chain sequences, expressed protein, development of chimeric IgE antibodies, and production of species-specific anti-IgE reagents. Application of ELISA and Western blotting has replaced the passive cutaneous anaphylaxis test for demonstration of antigen-specific IgE in serum. Regulation of the IgE response is complex, and its dependence on induction of T helper cell type 2 cytokines is now established. The next frontier in IgE research, as for many inherited diseases, lies in understanding the genetic make-up of the animal and which genes are important in controlling the IgE response.

Animals↗

PubMed2001

Extended allergen exposure in asthmatic monkeys induces neuroplasticity in nucleus tractus solitarius.

BACKGROUND: Extended exposure to allergen exacerbates asthma symptoms, in part via complex interactions between inflammatory cells and mediators. One consequence of these interactions is the triggering of local and central nervous system (CNS) neuronal activity that might further exacerbate the asthma-like symptoms by causing bronchoconstriction, mucous secretion, increased microvascular leak, and cough. One CNS region that might be particularly important is the caudomedial nucleus tractus solitarius (NTS). NTS neurons not only integrate primary afferent inputs from lung sensory nerve fibers but also have direct exposure to inhaled allergens and allergen-induced blood-borne inflammatory mediators via a deficient blood-brain barrier. Given the capacity of CNS neurons to undergo plasticity, allergen-induced changes in NTS neuronal properties could contribute to the exaggerated respiratory responses to extended allergen exposure. OBJECTIVE: In a recently developed rhesus monkey model of allergic asthma, we tested the hypothesis that extended exposure to allergen increases the intrinsic excitability of NTS neurons. METHODS: Three adult monkeys were sensitized and then repeatedly exposed to aerosols of house dust mite allergen; 4 monkeys served as controls. Whole-cell current-clamp recordings were made to measure 3 indices of excitability: resting membrane potential, input resistance, and number of action potentials evoked by current injections. RESULTS: Extended allergen exposure depolarized the resting membrane potential by 14% and increased the number of action potentials evoked by current injections (5-fold). CONCLUSION: The finding that NTS neurons in a primate model of allergic asthma undergo intrinsic increases in excitability suggests that CNS mechanisms might contribute to the exaggerated symptoms in asthmatic individuals exposed to allergen.

Allergens↗

PubMed2000

Haemophilus somnus-induced IgE in calves vaccinated with commercial monovalent H. somnus bacterins.

The ability of commercially available Haemophilus somnus bacterins to elicit an immunoglobulin E (IgE) response was examined in healthy calves using enzyme-linked immunosorbent assay (ELISA) and western blotting techniques. Thirty five calves were utilized in this study. Calves in Group 1 (n=7) did not receive any H. somnus vaccination and served as negative controls. Calves in each of Groups 2-5 (n=7 each) were vaccinated on days 0 (primary) and 14 (booster) with one of four commercially available H. somnus bacterins. Sera were harvested on days 0 and 14 and at weekly intervals for a total of 45 days. Sera were tested for the presence of IgE antibodies using a bovine IgE-specific ELISA. Low levels of H. somnus-specific IgE were detected by ELISA in all animals prior to the initiation of the study. All bacterins induced IgE levels that were significantly higher than control levels. Two bacterins elicited higher IgE levels at all time points. Sera were adsorbed against washed whole cells of either Salmonella typhimurium, P. multocida, or H. somnus or extracts of H. somnus. ELISA absorbance values were significantly decreased by adsorption with washed whole cells or extracts of H. somnus, whereas adsorption with other gram-negative bacteria only minimally decreased ELISA absorbance values. These results indicate that commercially available H. somnus bacterins can induce IgE antibody as early as 14 days post-vaccination. This IgE can be detected 45 days after the primary vaccination. Results also indicate that H. somnus-specific IgE antibodies can be found in serum of some cattle, possibly induced by existing or previous sensitization.

Adsorption↗

PubMed2000

Bovine respiratory syncytial virus-specific IgE is associated with interleukin-2 and -4, and interferon-gamma expression in pulmonary lymph of experimentally infected calves.

OBJECTIVE: To study the local immune response of calves to bovine respiratory syncytial virus (BRSV) infection with emphasis on IgE production and cytokine gene expression in pulmonary lymph. ANIMALS: Twelve 6- to 8-week-old Holstein bull calves. Six similar control calves were mock infected to obtain control data. PROCEDURE: Lymphatic cannulation surgery was performed on 12 calves to create a long-term thoracic lymph fistula draining to the exterior. Cannulated calves were exposed to virulent BRSV by aerosol. Lymph fluid collected daily was assayed for BRSV and isotype-specific IgE antibody, total IgG, IgA, IgM, and protein concentrations. Interleukin-4 (IL-4), interleukin-2 (IL-2), and interferon-gamma were semi-quantitated by reverse transcription-polymerase chain reaction (RT-PCR). Cell counts and fluorescence-activated cell scanner (FACSCAN) analysis of T-cell subsets were performed on lymph cells. RESULTS: Calves had clinical signs of respiratory tract disease during days 5 to 10 after infection and shed virus. Bovine respiratory syncytial virus-specific IgE in infected calves was significantly increased over baseline on day 9 after infection. Mean virus-specific IgE concentrations strongly correlated with increases in severity of clinical disease (r = 0.903). Expression of IL-2, IL-4, and interferon-gamma was variably present in infected and control calves, with IL-4 expression most consistent during early infection. CONCLUSIONS AND CLINICAL RELEVANCE: Infection with BRSV was associated with production of BRSV-specific IgE, and IL-4 message was commonly found in lymph cells of infected calves. This finding supports the concept that BRSV-induced pathophysiology involves a T helper cell type-2 response. Effective therapeutic and prophylactic strategies could, therefore, be developed using immunomodulation to shift the immune response more toward a T helper cell type-1 response.

Animals↗

PubMed1999

Interferon gamma production during bovine respiratory syncytial virus (BRSV) infection is diminished in calves vaccinated with formalin-inactivated BRSV.

Formalin-inactivated respiratory syncytial virus (FI-RSV) vaccination has been associated with severe disease in humans. Research in mice suggests that FI-RSV may prime for decreased interferon gamma (IFN-gamma) production at subsequent infection. Interferon-gamma production by peripheral blood mononuclear cells (PBMC) was measured following challenge of calves vaccinated with FI-BRSV to determine whether a similar mechanism is operative in a host naturally susceptible to RSV. Eight-week old male Holstein calves were administered FI-BRSV and mock challenge (V/M, n = 6); mock vaccination and BRSV challenge (M/C, n = 6) or FI-BRSV and BRSV challenge (V/C, n = 7). Vaccine was administered twice at a 2-week interval; challenge followed one month later. On days 0, 5 and 10 postchallenge (PC), PBMC were stimulated in vitro for 24 h with live BRSV, concanavalin A (positive control) or spent media (negative control). Supernatants were assayed for IFN-gamma using ELISA. Interferon-gamma production by BRSV-stimulated PBMC was increased in M/C and V/C calves as compared to V/M calves on day 5 PC (p < 0.015); and increased in M/C calves compared to V/C and V/M calves on day 10 PC (p < 0.015). Over time postchallenge, a significant increase in IFN-gamma production by BRSV-stimulated PBMC was seen in M/C calves (p < 0.025) but not in V/C calves. FI-BRSV vaccination of calves led to diminished IFN-gamma production postchallenge. Decreased IFN-gamma production may have contributed to impaired viral clearance and enhanced disease in FI-BRSV vaccinated calves.

Animals↗

PubMed1999

IgE responses to bluetongue virus (BTV) serotype 11 after immunization with inactivated BTV and challenge infection.

To test the hypothesis that development of a BTV-specific IgE response plays a role in clinical disease manifestation, the humoral immune response of cattle to inactivated and virulent BTV was studied. Three calves received three sensitizing immunizations of inactivated BTV, 3 weeks apart. The BTV-sensitized animals, two non-sensitized BTV-seropositive and 4 BTV-seronegative control cattle. were challenge-exposed with BTV-11, UC8 strain. All cattle inoculated with inactivated BTV developed group-specific non-neutralizing and serotype-specific neutralizing antibodies. The development of post-challenge-exposure neutralizing antibody titers was inversely correlated with protective immunity. None of the BTV-challenged animals showed clinical disease. The levels of IgE were greatest in the sensitized calves after virus challenge in comparison with control groups. The sequential development, specificity and intensity of virus protein-specific humoral responses were evaluated using immunostaining. After challenge exposure of BTV-sensitized and non-sensitized cattle, total and IgE antibodies reacted consistently within BTV structural proteins VP2, VP5 and VP7. Although no correlation was found between clinical disease and IgE, results add support to the hypothesis that IgE may be involved in the pathogenesis of clinical disease, since infection with BTV causes an increase in serum IgE levels. However, these results suggest that the levels of virus-specific reactivity may be an important factor in determining whether or not clinical disease manifestation occurs.

Animals↗

PubMed1999

Evaluation of severe disease induced by aerosol inoculation of calves with bovine respiratory syncytial virus.

OBJECTIVE: To develop a model of bovine respiratory syncytial virus (BRSV) infection that induces severe disease similar to that seen in some cattle with naturally acquired BRSV infection. ANIMALS: 25 male Holstein calves, 8 to 16 weeks old. PROCEDURE: 17 calves were given a low-passage field isolate of BRSV by aerosolization; 8 control calves were given supernatant from noninfected cell culture. Disease was characterized by evaluating clinical signs, virus isolation and pulmonary function tests, and results of blood gas analysis, gross and histologic postmortem examination, and microbiologic testing. RESULTS: Cumulative incidence of cough, harsh lung sounds, adventitious sounds, and dyspnea and increases in rectal temperature and respiratory rate were significantly greater in infected calves. Three infected calves developed extreme respiratory distress and were euthanatized 7 days after inoculation. Virus was isolated from nasal swab specimens from all infected calves but not from mock infected calves. On day 7 after inoculation, mean PaO2 and PaCO2 were significantly lower, and pulmonary resistance was significantly higher, in infected calves. During necropsy, infected calves had varying degrees of necrotizing and proliferative bronchiolitis and alveolitis with syncytial formation. The 3 calves euthanatized on day 7 had emphysematous bullae in the caudal lung lobes; 1 had unilateral pneumothorax. CONCLUSION AND CLINICAL RELEVANCE: Severe disease similar to that seen in some cattle with naturally acquired BRSV infection can be induced in calves with a single aerosol exposure of a low-passage clinical isolate of BRSV. Our model will be useful for studying the pathogenesis of BRSV infection and for evaluating vaccines and therapeutics.

Aerosols↗